Effect of metabolic inhibition on the activity of L-type Ca2+ channels in the presence of non-hydrolysable ATP analogs
Abstract
The effect of the protonophore FCCP. an uncoupler of oxidative phosphorylation, was examined on beta-adrenergic receptors agonist isoprenaline (ISO) stimulated L-type Ca2+ current (ICa) in frog ventricular myocytes dialyzed with an intracellular solution containing 3 mM ATP. FCCP dose-dependently
and reversibly inhibited the ISO ( 1 µM) stimulated ICa. FCCP (0.1 µM) reduced the ISO-stimulated ICa by 87 +/- 1% (p<0.05, n=4). FCCP (0.1 µM) also strongly inhibited ICa when 3 mM ATP-gamma-S was added to intracellular solution (by 78.9% =/- 3.6%, n=4, p<0.05), whereas the substitution of ATP by 3 µM AMP-PCP and 0.5 mM ATP-gamma-S completely abolished the FCCP-induced inhibition of ICa. Our results demonstrate that the suppression of the activity of L-type Ca2+ channels during metabolic inhibition is caused by ATP hydrolysis and this effect is not related with decreased protein phosphorylation.